0000000000114854

AUTHOR

Catherine Ledent

showing 3 related works from this author

Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.

2007

The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher…

Central Nervous SystemCannabinoid receptorEncephalomyelitis Autoimmune Experimentalmedicine.medical_treatmentEncephalomyelitisT-LymphocytesInflammationApoptosisMice TransgenicBiologyGeneral Biochemistry Genetics and Molecular BiologyReceptor Cannabinoid CB2MiceReceptor Cannabinoid CB1medicineCannabinoid receptor type 2AnimalsCell ProliferationDNA PrimersAutoimmune diseaseNeuronsExperimental autoimmune encephalomyelitisGeneral Medicinemedicine.diseaseEndocannabinoid systemImmunohistochemistryImmunologyEncephalitislipids (amino acids peptides and proteins)Cannabinoidmedicine.symptomNature medicine
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Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists

2014

The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery. Procedures included identification of chemicals and modeling to predict the mode of exclusion; induction and control of spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the mechanism of CNS-exclusion via drug pumps; genome-wide association study in N2(129×ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing…

Central Nervous SystemCannabinoid receptorEncephalomyelitis Autoimmune ExperimentalMultiple Sclerosismedicine.medical_treatmentCentral nervous systemPharmacologyBiologyBiochemistryMiceReceptor Cannabinoid CB1GeneticsmedicineAnimalsSpasticityMolecular BiologyCannabinoid Receptor AgonistsCannabinoidsMultiple sclerosisExperimental autoimmune encephalomyelitisCannabinoid Receptor Agonistsmedicine.disease3. Good healthmedicine.anatomical_structureAjulemic acidMuscle SpasticityFemaleCannabinoidmedicine.symptomMultidrug Resistance-Associated ProteinsBiotechnologymedicine.drug
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Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway.

2014

Abstract Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC–Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC–Treg clusters, indicating a ro…

AdenosineRegulatory T cellT cellImmunologyMedizinchemical and pharmacologic phenomenaCell CommunicationBiologyT-Lymphocytes RegulatoryMiceAdenosine TriphosphateAntigens CDCell MovementmedicineImmunology and AllergyAnimalsGuanine Nucleotide Exchange FactorsDendritic cell migrationReceptors Adenosine A2Apyraserap1 GTP-Binding Proteinshemic and immune systemsDendritic CellsActin cytoskeletonAdenosineAdenosine receptorCell biologyActin Cytoskeletonmedicine.anatomical_structureRap1Signal transductionmedicine.drugSignal TransductionJournal of immunology (Baltimore, Md. : 1950)
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